IN-VIVO CARDIOVASCULAR REACTIVITY AND BAROREFLEX ACTIVITY IN DIABETICRATS

Objectives: Abnormalities of the cardiovascular system, e.g. impaired vasoreactivity and changes in baroreflex control of heart rate, are kn own to occur in experimental diabetes. It is not clear whether these c ardiovascular dysfunctions are direct consequences of cardiovascular d eficits and/or have autonomic neuropathy as a cause. Methods: To diffe rentiate between cardiovascular deficits or neuronal impairment as a c ause for these cardiovascular dysfunctions, we tested the effects of t he ACTH(4-9) analogue, Org 2766, a neurotrophic compound without cardi ovascular effects, on arterial pressure, heart rate and baroreflex con trol of heart rate. At 15 weeks, rats were made diabetic by injection of streptozotocin, and from 0-6, 6-12 or 12-18 weeks thereafter 3 grou ps of rats were treated with Org 2766. These effects were evaluated du ring phenylephrine-induced increases, and sodium nitroprusside-induced decreases, in blood pressure, in rats that had been diabetic for vari ous periods (2-42 weeks). Results: Throughout, both depressor response and maximal vasodilator activity in response to sodium nitroprusside were significantly (P < 0.05) reduced as compared to those of the non- diabetic controls. The presser response of the diabetic rats to phenyl ephrine was only significantly (P < 0.05) reduced at 4, 6 and 12 weeks , and at 18 weeks, the diabetic rats were either hypo- or normorespons ive; Org 2766 did not restore the disturbed presser response. From wee ks 4 to 42 both maximal decrease in heart rate and sensitivity of baro reflex-mediated bradycardia in the diabetic rats were significantly le ss (P < 0.05) than those in the non-diabetic controls. Org 2766 restor ed the diminished baroreflex-mediated bradycardia of diabetic rats to non-diabetic control levels at 6 weeks, had an ameliorating effect at 12 weeks and no effect at 18 weeks. Conclusions: Time-dependent decrea ses in baroreflex sensitivity in diabetic rats was demonstrated and a much less steep decline of baroreflex sensitivity occurred in non-diab etic control rats. The ACTH(4-9) analogue, Org 2766, when given immedi ately upon the induction of diabetes seem to delay the development of autonomic neuropathy, which suggests that cardiovascular factors appea r to be of minor importance. (C) 1998 Elsevier Science B.V. All rights reserved.